Trabecular bone score and bone mineral density in patients with long-term controlled acromegaly.

OBJECTIVE: Acromegaly is associated with increased vertebral fracture (VFs) risk not correlated to bone mineral density (BMD). Trabecular bone score (TBS), related to bone microarchitecture, provides information on bone strength. This cross-sectional study considered the usefulness of TBS and BMD to assess bone status in long-term controlled acromegalic patients. DESIGN, PATIENTS, MEASUREMENTS: 26 acromegaly patients (14 female and 12 males) were included in the study. A further 117 subjects were recruited as controls (58 females and 57 males). BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was obtained applying Medimaps software 2.0. Biochemical parameters were determined by standardized techniques. RESULTS: 73% of patients with acromegaly exhibited normal lumbar spine (LS) BMD. TBS was normal in 38% of acromegalic patients and partially degraded or degraded in 31% of patients, respectively. No differences were found in LS BMD between acromegalic patients and controls. TBS values were significantly lower in patients with acromegaly (1.27 ± 0.13 vs. 1.35 ± 0.17, p = .01). Postsurgical remission was associated with higher TBS values (1.35 ± 0.10 vs. 1.23 ± 0.13, p = .02) and pituitary radiotherapy treatment with lower TBS values (1.18 ± 0.12 vs. 1.31 ± 0.12, p = .004). On multivariate analysis, age, BMI and LS BMD were predictors of TBS changes in patients with acromegaly (p < .05). CONCLUSIONS: Patients with long-term controlled acromegaly can exhibit deterioration of bone microstructure measured with TBS, despite BMD measurement not showing bone loss. Our study suggests that TBS is useful for monitoring the bone status changes in acromegalic patients.

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

Trabecular bone score in patients with liver transplants after 1 year of risedronate treatment.

The aim of this study was to analyse the effect of risedronate on Trabecular Bone Score in liver transplant patients with low bone mass, during 1-year follow-up. In this retrospective cohort study, trabecular bone score (TBS) was calculated from dual X-ray absorptiometry images of the lumbar spine (LS), collected from a prospective randomized open-label 1-year trial performed in liver recipient patients. A total of 89 patients with osteopenia or osteoporosis were randomized to receive RIS plus calcium and vitamin D3 or calcium and vitamin D3. TBS was low in both groups at baseline, 6 and 12 months. Baseline TBS at the LS showed degraded microarchitecture in 22.8% of patients, partially degraded in 40.3%, and normal values in 36.8% of the patients. After 1 year of treatment, no difference in TBS was observed between both groups. No correlations were found between bone mineral density (BMD) and TBS values at any follow-up time point. No relationship was found between BMD, TBS or immunosuppressive drugs with incidental fracture. No significant effect in TBS was observed in liver transplant patients treated with RIS or calcium and vitamin D3 after 1 year of follow-up. In these patients, the clinical usefulness of this new tool should be established.

Bone loss after heart transplant: effect of alendronate, etidronate, calcitonin, and calcium plus vitamin D3.

OBJECTIVE: To compare the effects of calcitonin, etidronate, and alendronate in preventing bone loss during the first 2 years after heart transplant. METHODS: A total of 222 heart transplant recipients (mean [SD] age, 52.4 [10] years, 85% male) were evaluated. Patients with normal bone mineral density (reference group, n = 102) received 1000 mg/d calcium plus 800 IU/d vitamin D3. The rest were assigned to 200 IU/d of calcitonin (n=42), 400 mg/d etidronate orally for 14 days quarterly (n = 33), or 10 mg/d alendronate (n = 45). All patients received calcium and vitamin D. Bone mineral density was assessed by dual-energy x-ray absorptiometry in the lumbar spine, the entire femur, and the femoral neck at baseline and 6, 12, and 24 months after transplant. RESULTS: At 2 years after transplant, bone mineral density in the lumbar spine had decreased in the reference group (-3.07%), calcitonin group (-0.93%), and etidronate group (-1.87%) but not in the alendronate group (+4.9%; P <.001). After 2 years, bone mineral density in the entire femur decreased in all groups (-3.2% in the reference group, -3.6% in the calcitonin group, -4.6% in the etidronate group, and -0.5% in the alendronate group) but bone loss was significantly lower in the alendronate group (P <.001). Bone mineral density in the femoral neck also decreased in all groups. The incidence of vertebral fractures did not differ among groups. Adverse events were similar between groups. CONCLUSIONS: Alendronate therapy in heart transplant recipients was associated with a significant increase in bone mineral density in the lumbar spine and less bone loss at the hip.

Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single-center study.

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D(3) 800 IU/day (n = 45) or calcium and vitamin D(3) at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum ß-CrossLaps (ß-CTX) and procollagen type 1 amino-terminal peptide (P1NP) and fracture rate. Spine X-rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum ß-CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.

Ethnicity Strongly Influences Body Fat Distribution Determining Serum Adipokine Profile and Metabolic Derangement in Childhood Obesity.

Background: Body fat content and distribution in childhood is influenced by sex and puberty, but interethnic differences in the percentage and distribution of body fat also exist. The abdominal visceral/subcutaneous fat ratio has been the main feature of body fat distribution found to associate with the serum adipokine profile and metabolic derangement in adulthood obesity. This has also been assumed for childhood obesity despite the known singularities of this disease in the pediatric age in comparison to adults. Objective: We aimed to investigate the effect of ethnicity, together with sex and pubertal status, on body fat content and distribution, serum adipokine profile, metabolic impairment and liver steatosis in children and adolescents with obesity. Patients and Methods: One hundred and fifty children with obesity (50% Caucasians/50% Latinos; 50% males/50% females) were studied. Body fat content and distribution were studied by whole body DXA-scan and abdominal magnetic resonance, and their relationships with liver steatosis (as determined by ultrasonography), glycemia, insulinemia, lipid metabolism, uric acid, total and HMW-adiponectin, leptin, leptin-receptor, and sex steroid levels were explored. Results: Latino patients had more severe truncal obesity (higher trunk/lower limb fat ratio, odds ratio 10.00; p < 0.05) and higher prevalence of liver steatosis than Caucasians regardless of sex or pubertal status, but there were no difference in the visceral/subcutaneous abdominal fat ratio, except for pubertal females. A higher trunk/lower limb fat ratio, but not the visceral/subcutaneous abdominal fat ratio, was associated with adipokine profile impairment (higher free leptin index and lower adiponectin levels), insulin resistance and dyslipidemia, and was further enhanced when liver steatosis was present (p < 0.05). A higher abdominal visceral/subcutaneous fat ratio was observed in prepubertal children (p < 0.01), except for Latino females, whereas predominant subcutaneous fat deposition was observed in adolescents. Conclusion: Ethnicity is one of the main determinants of increased trunk body fat accumulation in Latino children with obesity, which is best estimated by the trunk/lower limb fat ratio and related to the development of metabolic derangement and liver steatosis.

A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review.

BACKGROUND: Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. METHODS: We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. RESULTS: Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. CONCLUSION: The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors.

[Prevalence of deficient and insufficient vitamin D levels in a young healthy population]. / Prevalencia de concentraciones deficientes e insuficientes de vitamina D en una población joven y sana.

BACKGROUND AND OBJECTIVES: Recent studies have shown a high frequency of insufficient serum vitamin D levels in the general population, especially in the elderly and in individuals with osteoporosis. Data from the young adult population are scarce, but also reveal a high prevalence of vitamin D insufficiency and deficiency in this age group. The main reasons for this high prevalence seem to be poor dietary vitamin D intake and low sun exposure. The aim of the present study was to determine the prevalence of vitamin D insufficiency and deficiency in a young healthy population and its association with concentrations of calcium and parathyroid hormone and sun exposure. METHODS: We performed an observational, descriptive study in 116 subjects (38 men and 78 women aged 26.56 +/- 3.32 years), during the late spring and early summer of 2007. Fasting blood samples were obtained and levels of 25-hydroxivitamin D, intact parathyroid hormone, calcium, albumin and creatinine were measured. A questionnaire designed to assess sun exposure and sunshine protection during the previous 12 months was administered. RESULTS: The mean value of 25-hydroxivitamin D obtained was 24.58 +/- 6.98 ng/ml. The subjects were divided into three groups according to 25-hydroxivitamin D levels: deficient: < 20 ng/ml (27.58%); insufficient: 20-30 ng/ml (56.03%); and sufficient: > or = 30 ng/ml (16.37%). No statistically significant differences were found between the groups or the studied variables except for age in relation to vitamin D levels. CONCLUSIONS: Our study shows a high prevalence of vitamin D insufficiency in a young healthy population with no clear relationship with sun exposure or sunscreen protection. The low intake of food rich in vitamin D and the lack of food fortification combined with scarce effective sun exposure could account for the low serum levels of vitamin D in this population.

[Lumbar pain and bilateral adrenal masses]. / Dolor lumbar y masas adrenales bilaterales.

Many problems may arise when defining whether adrenal lesions are primary to the adrenal glands or represent other tissue, whether they are benign or malignant and whether they are functioning or nonfunctioning. Adrenal imaging complements the clinical and hormonal evaluation of these patients. We present a patient with lumbar pain and bilateral adrenal masses.

Regional skeletal bone deficit in female adolescents with anorexia nervosa: influence of the degree of malnutrition and weight recovery in a two year longitudinal study.

AIM: To analyze changes in bone mineral density (BMD) and the effect of weight recovery on the restoration of bone mass in adolescent females with anorexia nervosa (AN) with moderate malnutrition. STUDY DESIGN: We evaluated lumbar and femoral BMD in 27 females with restrictive AN with malnutrition and amenorrhea for over (M+PA) or less than (M+SA) one year and 12 with normal nutrition and amenorrhea for over one year (N+PA) followed for 24 months. RESULTS: BMI remained below -1.5 SD in M+PA and increased at 24 months in M+SA. M+PA had low lumbar and femoral neck BMD at diagnosis, decreasing at 24 months. Lumbar BMD in N+PA and M+SA was reduced, with an increase in M+SA at 24 months. CONCLUSIONS: Moderate malnutrition in AN induces loss of bone mass at the lumbar and femoral levels. Weight gain and resumption of menses increases bone mass, especially in the lumbar spine.

Alendronate with and without cholecalciferol for osteoporosis: results of a 15-week randomized controlled trial.

OBJECTIVE: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg alone (ALN). METHODS: This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357). MAIN OUTCOME MEASURES: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross-links (NTX). RESULTS: Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). CONCLUSION: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.

Detection of ketonemia and its relationship with hyperglycemia in type 1 diabetic patients.

The aims of this study were to assess the prevalence of ketosis in type 1 diabetic patients with casual hyperglycemia (>250 mg/dl), to establish the relationship between glycemia and ketonemia during daily life, and to determine the utility of ketonemia. Capillary glycemia levels from 562 type 1 diabetic patients were recorded. Prevalence of casual hyperglycemia was 27.58%, and prevalence of asymptomatic ketonemia was 8.39%. Regarding blood ketone levels, 110 out of 155 patients (70.96%) had blood ketone levels of between 0 and 0.1 mmol/l and 32 out of 155 patients (20.63%) had blood ketone levels of between 0.2 and 0.4 mmol/l. Surprisingly, the mean glycemia levels in these subgroups did not differ and was consistently high (around 300 mg/dl), leading to the observation that even ketone levels considered as non-pathologic should probably be taken into account for a proper diabetes control. Some discrepancies between quantitative determination of ketonuria and qualitative determination of ketonemia were observed. That is in 20 patients with positive ketonuria, ketonemia was not detected, probably because ketosis was already resolved. Asymptomatic ketosis was observed in the hyperglycemic type 1 diabetic population, and metabolic control of these patients with a point of care device is recommended, together with a subsequent revision of insulin treatment. Furthermore, this study supports the opinion that the presence of ketosis, detected by beta-OHB levels, even below levels considered as pathologic, together with hyperglycemia, must be taken into account for proper monitoring and therapeutic control of diabetic patients.

Quantitative ultrasound of the calcaneus in long-term liver or cardiac transplantation patients.

Bone loss is one of the most common complications after solid-organ transplantation, but it is frequently under-diagnosed. Our purpose was to evaluate quantitative ultrasound of calcaneus (QUS) in comparison with dual-energy X-ray absorptiometry (DXA) to identify transplant recipients with osteoporosis. We have cross-sectionally evaluated 140 transplant recipients (85 liver and 55 cardiac transplantations; mean age: 53.6 years, time since transplantation: 67.9 months). Devices used were Hologic 4500 QDR for DXA measurements and Sahara Clinical Sonometer (Hologic Inc, Bedford, MA) for calcaneal QUS. Quantitative ultrasound index (QUI) was calculated from speed of sound (m/s) and broadband ultrasonic attenuation (dB/MHz). QUI T-score and bone mineral density (BMD) T-score (spine and hip) were obtained from Spanish normative data. According to World Health Organization criteria, defined either at lumbar spine or femoral neck, 61% of the females had osteopenia and 32% had osteoporosis, whereas 52% of the males had osteopenia and 11% had osteoporosis. Calcaneal QUS parameters (speed of sound, broadband ultrasonic attenuation, and QUI) were positively correlated with lumbar and femoral BMD (p<0.001). In receiver operator characteristic analysis, a T-score QUI

Seven years of follow up of trabecular bone score, bone mineral density, body composition and quality of life in adults with growth hormone deficiency treated with rhGH replacement in a single center.

BACKGROUND: Adult growth hormone deficiency (AGHD) is characterized by impaired physical activity, diminished quality of life (QoL), weight and fat mass gain, decreased muscle mass and decreased bone mineral density (BMD). The aim of this study was to evaluate the effects of long-term treatment (7 years) with recombinant human growth hormone (rhGH) on metabolic parameters, body composition (BC), BMD, bone microarchitecture and QoL. PATIENTS AND METHODS: In this prospective study, BMD and BC were assessed by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was assessed with the trabecular bone score (TBS). The QoL-AGHDA test was used to assess QoL. RESULTS: A total of 18 AGHD patients (mean age, 37.39 ± 12.42) were included. Body weight and body mass index (BMI) showed a significant increase after 7 years (p = 0.03 and p = 0.001, respectively). There was a significant tendency of body fat mass (BFM) (p = 0.028) and lean body mass (LBM) (p = 0.005) to increase during the 7 years of rhGH treatment. There was a significant increase in lumbar spine (LS) BMD (p = 0.01). TBS showed a nonsignificant decrease after 7 years of treatment, with a change of -0.86% ± 1.95. QoL showed a large and significant improvement (p = 0.02). CONCLUSION: Long-term rhGH treatment in AGHD patients induces a large and sustained improvement in QoL. Metabolic effects are variable with an increase in LBM as well as in BMI and BFM. There is a positive effect on BMD based on the increase in LS BMD, which stabilizes during long-term therapy and is not associated with a similar increase in bone microarchitecture.

Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency.

CONTEXT: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established. CASE DESCRIPTION: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 µg/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment. CONCLUSION: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency.

Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability.

Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.

Is increasing urinary albumin a better marker for microvascular than for macrovascular complication of type 2 diabetes mellitus?

AIMS: The aims of the study were to evaluate the prevalence of increased urinary albumin excretion (UAE) and associated cardiovascular risk factors and vascular diabetes complications in patients with type 2 diabetes mellitus (DM). METHODS: We studied 975 patients in a cross-sectional design from 1998 to 2000. Frequency of micro- and macroalbuminuria, and their associations with cardiovascular risk factors and vascular DM complications, were examined. RESULTS: Prevalence of increased UAE was 28.5% (18.3% micro- and 10.2% macroalbuminuria). Body mass index (BMI) (only females) and hemoglobin (Hb)A1c significantly correlated with macroalbuminuria (p = 0.034, p = 0.027, respectively), while high blood pressure (diastolic) was associated with microalbuminuria (p = 0.008). Diabetes duration, high systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were significantly correlated with both micro- and macroalbuminuria. Increased UAE was associated with neuropathy (relative risk (RR) 2.12, confidence interval (CI) 1.07-4.19), retinopathy (RR 2.19, CI 1.76-2.74) and hypertension (RR 2.91, CI 1.77-4.78), but not with cardiovascular disease, high cholesterol and peripheral vascular disease. In the multiple logistic regression analysis, a significant association of albuminuria was found with diabetes duration (odds ratio (OR) 1.59, CI 0.98-2.58; p < 0062), hypertension (OR 3.42, CI 2.22-5.27; p < 0.0001), low HDL cholesterol (OR 1.78, CI 1.31-2.43; p < 0.0003), current smoking status (OR 2.19, CI 1.32-3.64; p < 0.0024), and increased serum creatinine (OR 11.16, CI 5.7-21.7; p < 0.0001). CONCLUSION: Prevalence of increased UAE was similar to that described in other geographically close populations. The stronger association found with microvascular diabetes complications suggests that increased UAE is a better predictor for renal damage than for cardiovascular disease in this type 2 DM population.

A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus.

OBJECTIVE: The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia. METHODS: Patients with type 2 diabetes mellitus (HbA(1c) >/=6.5% and /=7% to <8%) or high (>/=8% to

Bone mineral density and vitamin D levels in erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare disease with painful cutaneous photosensitivity, in which patients are recommended to avoid sun exposure, and wear sunscreen and adequate clothing. Our aim was to study bone mineral density (BMD) and other mineral parameters, including serum 25(OH)D levels, to evaluate the impact of these measures in the follow-up of EPP patients. A cross-sectional study of ten EPP patients (median age 25; range 22-55, four males and six females), was performed evaluating clinical features, biochemical values (bone markers and serum 25 hydroxyvitamin D), and BMD. Median serum 25(OH)D level was 19.65 ng/ml [17.50; 24.80]. Four patients had 25(OH)D in insufficiency range (20-30 ng/ml) and five patients in the deficiency range (<20 ng/ml). Lumbar T-score median levels were in the osteopenia range in both females (-1.50 [-2.30; -1.0]) and males (-1.90 [-2.40; -0.70]). Also, in the female group median femoral neck T-score were in the osteopenia range (-1.20 [-1.60; -0.60]). This is the first study reporting low BMD in EPP patients. Osteoporosis, osteopenia, and vitamin D deficiency are frequent findings in EPP patients. The contribution of sunlight avoidance measures to these results remains to be clarified. Serum levels of protoporphyrins were not related to these alterations and other factors should be investigated. We suggest that the monitoring of serum vitamin D levels in EPP patients should be mandatory, as well as vitamin D and calcium supplementation.